影响P2Z受体介导慢性淋巴细胞白血病细胞凋亡的各种因素及其机理研究

目的　探讨嘌呤能 P2 Z受体介导慢性淋巴细胞白血病 (CL L )细胞凋亡的影响因素及其机理。方法　在二价阳离子—— 1.0 mm ol/L Mg2 + 、Zn2 + 、Ca2 + 、Sr2 + 、Co2 + 、Ba2 + ,不同浓度的 EDTA或 EGTA,不同温度及在含 15 0 mm ol/L胆碱的介质中 ,将表达 P2 Z受体 [P2 Z(+) ]的 CL L细胞分别同 1.0 mm ol/L三磷酸腺苷 (ATP)或 0 .1m mol/L苯甲酰苯甲酸 ATP(Bz ATP)体外培养 8小时 ,以 DNA凝胶电泳、Td T法和流式细胞分析 (FCA )检测上述条件下细胞凋亡的诱导或抑制效应。结果　 Mg2 + 或 Ca2 + 能以剂量依赖性方式促进 ATP诱导 P2 Z(+)细胞凋亡 ,而 EDTA或 EGTA却以相反的方式抑制 P2 Z(+)细胞凋亡的发生 ;1.0 mm ol/L Zn2 + 可完全阻止 ATP诱导 P2 Z(+)细胞凋亡所产生的 DNA片段 ,但其它二价阳离子包括 1.0 mm ol/L Sr2 + 、Co2 + 、Ba2 + 却不影响 ATP的诱导 ;胆碱作为磷脂酶 D(PL D)的抑制剂 ,也可部分抑制 P2 Z(+)细胞凋亡产生的 DNA片段 ;当温度低于 10℃ ,可完全阻止 ATP诱导 P2 Z(+)细胞凋亡产生 DNA片段的发生。结论　 P2 Z受体介导 CL L细胞凋亡可能与核酸内切酶 ,PL D的参与密切相关。     

c—myc反义寡核苷酸对白血病细胞凋亡的影响

目的 研究c-myc反义寡核苷酸对白血病细胞凋亡的影响。方法 用针对c-myc mRNA 5'端非翻译区的一个18bp的反义寡核苷酸与HL60细胞、分离的急性粒细胞白血病病人白细胞共培养10h,用凋亡细胞计数、DNA凝胶电泳、ELISA、流式细胞仪等方法测白血病细胞的调亡。结果 c-myc反义寡核苷酸能够诱导HL60细胞凋亡,且此作用随着作用浓度的提高而增加;此反义核酸只诱导白血病患者的白血病细胞凋亡,对正常白细胞的凋亡无影响。结论 c-myc反义核酸可以通过诱导白血病细胞凋亡来治疗急性粒细胞白血症,且该作用的特异性好。     

白血病患者巨细胞病毒抗体检测及其临床意义初探

目的初步探讨白血病患者巨细胞病毒(HCMV)感染状况及HCMV抗体检测的应用价值.方法采用ELISA法对75例白血病患者和28名健康人HCMV抗体进行检测.其中有11例M3患者作化疗前后对比检测.结果白血病组HCMV-IgM抗体阳性率为2.7%,健康对照组为0;白血病组HCMV-IgG抗体水平较健康对照组显著(P＜0.01)或非常显著(P＜0.005)增高;如以HCMV-IgG抗体高于8.4IU/ml(约临界值1.1IU/ml的4倍)考虑为HCMV活动性感染,则白血病组阳性率35.7%,较健康对照组3.6%明显升高(P＜0.005),且M3化疗后阳性率有上升趋势.结论HCMV抗体检测有助于白血病患者HCMV感染的临床诊疗.     

诱导分化治疗中端粒酶活性的改变及其意义

目的研究诱导分化治疗中端粒酶活性的变化规律。方法对白血病细胞株、正常骨髓和急性白血病的骨髓单个核细胞的端粒酶活性进行了检测,观察了全反式维甲酸(ATRA)在体外和体内分化诱导过程中端粒酶活性的改变。结果发现端粒酶表达下调是诱导分化的早期效应之一。诱导分化治疗可使急性白血病M3早幼粒细胞端粒酶活性水平降至正常。结论在体内和体外实验中,ATRA诱导分化过程中伴随着端粒酶活性下调。     

急性白血病患者病情与D-二聚体含量相关性的研究

目的研究急性白血病患者病情与血浆Ｄ－二聚体含量的相关性及其临床意义。方法骨髓涂片在显微镜下按常规 分类计数 ５００个有核细胞,用凝血一期法测定凝血酶原时间／国际标准化比率（ＰＴ／ＩＮＲ）和活化的部分凝血活酶时间 （ＡＰＴＴ）,用乳胶凝集法测定Ｄ－二聚体含量。结果急性非淋巴细胞性白血病（ＡＮＬＬ）组与急性淋巴细胞性白血病 （ＡＬＬ）组的骨髓原始细胞加幼稚细胞数与同时期的凝血指标ＰＴ／ＴＮＲ、Ｄ－二聚体含量呈显著正相关,但ＰＴ／ＩＮＲ大都处 于正常范围,异常率低,而Ｄ－二聚体异常率较高,与骨髓原始加幼稚细胞数异常率有较好的一致性。结论Ｄ－二聚体含 量的变化可作为判断急性白血病病情变化的参考指标之一。     

Successful kidney transplantation in a patient with pre-existing chronic myeloid leukemia treated with imatinib

Active malignancy is an absolute contraindication to kidney transplantation. As for chronic myeloid leukemia (CML), a Philadelphia chromosome-positive myeloproliferative neoplasm, the introduction of tyrosine kinase inhibitors has transformed CML from a lethal into a manageable chronic disease with a close-to-normal life expectancy. To date it is unknown whether kidney transplantation can be safely performed in patients with pre-existing CML. We describe the clinical course of a 57-year-old male patient with chronic kidney disease caused by reflux nephropathy. This patient had undergone first kidney transplantation 20 years earlier and had again been on chronic hemodialysis for 6 years when CML was diagnosed. First-line therapy with 400 mg imatinib daily was well tolerated and induced an optimal cytogenetic and molecular response 3 months after initiation. One and a half years after CML diagnosis, a second kidney transplantation from a deceased donor was performed. Immunosuppression included basiliximab, tacrolimus, mycophenolate mofetil, and corticosteroids. Currently, 2 years posttransplant, renal allograft function is stable (serum creatinine 1.09 mg/dL, estimated glomerular filtration rate 75 mL/min per 1.73 m²), and CML remains in deep molecular remission with imatinib. Imatinib-treated CML in deep molecular remission could be regarded as inactive malignancy and may therefore not be viewed as an absolute contraindication to kidney transplantation.     

Peliosis lienalis with atraumatic splenic rupture in a patient with chronic myelomonocytic leukemia: A case report

IntroductionAtraumatic splenic rupture is a rare but life-threatening condition which may be associated with hematological malignancies.Presentation of caseWe present the case of a 63-year-old male patient with a history of chronic myelomonocytic leukemia and sarcoidosis under therapy with prednisone, who suffered an atraumatic splenic rupture with hemodynamic instability. He was managed with proximal splenic artery embolization and secondary open splenectomy. On pathology the diagnosis of peliosis lienalis was established.DiscussionPeliosis is a rare pathological entity, which presents with multiple blood-filled cavities within parenchymatous organs and is of unknown etiology and pathogenesis. In retrospect a rapid increase in splenomegaly and inhomogeneous parenchyma of the spleen on sonography was realized.ConclusionSonographic changes in size and parenchyma of the spleen in patients with hematological malignancies might help suspecting peliosis lienalis with impending splenic rupture and could alter clinical management towards a prophylactic splenectomy.     

Elucidating chromatin and nuclear domain architecture with electron spectroscopic imaging

Electron microscopy has been the ‘gold standard’ of spatial resolution for studying the structure of the cell nucleus. Electron spectroscopic imaging (ESI) offers advantages over conventional transmission electron microscopy by eliminating the need for heavy-atom contrast agents. ESI also provides mass-dependent and element-specific information at high resolution, permitting the distinguishing of structures that are primarily composed of protein, DNA, or RNA. The technique can be applied to understand the structural consequences of epigenetic modifications, such as modified histones, on chromatin fiber morphology. ESI can also be applied to elucidate the multifunctional behavior of subnuclear ‘organelles’ such as the nucleolus and promyelocytic leukemia nuclear bodies. The authors dedicate this paper to the memory of Ying Ren (1961–2007). We all benefited from knowing her. Our research advanced through the technical creativity she provided.     

Allogeneic peripheral blood stem cell transplantation for leukemia

Objective To observe engraftment kinetics, the incidence and severity of graft-versus-ho st disease (GVHD), and clinical outcome on 40 recipients undergoing allogeneic p eripheral blood stem cell transplantation (allo-PBSCT).Methods From June 1997 to May 1999, forty leukemia patients with a median age of 35 year s underwent allo-PBSCT. PBSC were mobilized with G-CSF at a dose of 5 μg/kg s.c. every 12 hours for 5 days. A median of 7.7 (2.0-16.8)×10 (6) CD34(+) cells/kg was infused into the recipients. Busulfan-cyclophosphamid e (BU-CY) was used as the conditioning regimen. All patients received cyclospo rine A and either methotrexate (n=34) or methylprednisolone (n=6) for GVHD p rophylaxis. Results Engraftment of neutrophils and platelets was achieved at a median of 13 days (9 -28 days) and 12 days (7-60 days) respectively. Patients receiving ≥4×10 (6) CD34(+) cells/kg or given G-CSF post transplant had significantl y accelerated neutrophil and platelet engraftment. Acute GVHD occurred in 17 of 40 patients (42.5%), with grade Ⅱ-Ⅳ acute GVHD in 10 patients (25%). Chron ic GVHD developed in 21 (9 extensive, 12 limited) out of 30 evaluable patients ( 21/30, 70%) with a median follow up of 380 days (180-900 days). Transplan t related mortality was 17.5% and the relapse rate was 10%. The probability of leukemia free survival at 3 years was 72.5%.Conclusion Allo-PBSCT can provide rapid hematopoietic reconstitution without an increased incidence of acute GVHD, but may be associated with a high risk of chronic GVHD .